Methylsulfonylmethane

Because of its polarity and thermal stability, molten DMSO₂ has been used industrially as a high-temperature solvent. For example, displacement of aryl chlorides by potassium fluoride has been conducted in the liquid.{{cite book |doi=10.1002/047084289X.rd371 |chapter=Dimethyl Sulfone |title=Encyclopedia of Reagents for Organic Synthesis |year=2001 |last1=Hareau |first1=Georges |last2=Kocienski |first2=Philip | name-list-style = vanc |isbn=978-0471936237}}

With a pK_a of 31, the sulfone can be deprotonated with sodium amide. The conjugate base has been used as a nucleophile.

Methylsulfonylmethane is marketed as a dietary supplement with medical claims ranging from anti-inflammatory effects for pain management, skin condition and aging treatments, and immune system modulation.{{Cite journal |last1=Butawan |first1=Matthew |last2=Benjamin |first2=Rodney L. |last3=Bloomer |first3=Richard J. |date=2017-03-16 |title=Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement |journal=Nutrients |volume=9 |issue=3 |pages=290 |doi=10.3390/nu9030290 |doi-access=free |issn=2072-6643 |pmc=5372953 |pmid=28300758}}{{Cite book | vauthors = Jacob S, Lawrence RM, Zucker M |title=The Miracle of MSM: The Natural Solution for Pain |location=New York |publisher=Penguin-Putnam |year=1999}}{{cite journal |vauthors=Morton JI, Siegel BV |date=November 1986 |title=Effects of oral dimethyl sulfoxide and dimethyl sulfone on murine autoimmune lymphoproliferative disease |journal=Proceedings of the Society for Experimental Biology and Medicine |volume=183 |issue=2 |pages=227–30 |doi=10.3181/00379727-183-42409 |pmid=3489943 |s2cid=23242700}} No medical uses for MSM have been approved and there is limited evidence to support most of the claims.{{Citation needed|date=January 2025}}{{Cite journal |last1=Brien |first1=S. |last2=Prescott |first2=P. |last3=Bashir |first3=N. |last4=Lewith |first4=H. |last5=Lewith |first5=G. |date=2008-11-01 |title=Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis |url=https://www.sciencedirect.com/science/article/pii/S1063458408000666 |journal=Osteoarthritis and Cartilage |volume=16 |issue=11 |pages=1277–1288 |doi=10.1016/j.joca.2008.03.002 |pmid=18417375 |issn=1063-4584}} Small studies of MSM have suggested some benefit for treatment of oxidative stress and osteoarthritis, but evidence for other uses is lacking.{{cite web |title=MSM Monograph |url=https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=522 |access-date=10 Jan 2024 |website=Natural Medicines Comprehensive Database |publisher=Therapeutic Research Faculty}}{{subscription required}}

Methylsulfonylmethane may or may not be useful for osteoarthritis (OA) knee pain relief. Methodological issues with the clinical trials prevent firm conclusions, and the review authors stated: "No definitive conclusion can currently be drawn" and there is "no definitive evidence that MSM is superior to placebo in the treatment of mild to moderate osteoarthritis of the knee."{{cite journal |vauthors=Brien S, Prescott P, Bashir N, Lewith H, Lewith G |date=November 2008 |title=Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis |journal=Osteoarthritis and Cartilage |volume=16 |issue=11 |pages=1277–88 |doi=10.1016/j.joca.2008.03.002 |pmid=18417375 |doi-access=free}}

Multiple human and animal trials indicate MSM may reduce oxidative stress and inflammation.{{Citation needed|date=January 2025}}

In July 2007 a manufacturer of MSM submitted a notification to the U.S. FDA claiming generally recognized as safe (GRAS) status. GRAS status is for safety, and has no evaluation of efficacy. The FDA responded in February 2008 with a letter of non-objection, functionally designating OptiMSM, the branded form of MSM, as GRAS. The designation allows MSM to be added to processed foods.{{cite web |year=2008 |title=Agency Response Letter GRAS Notice No. GRN 000229 |url=https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm153891.htm |work=fda.gov}}

The {{LD50}} of MSM is greater than 17.5 grams per kilogram of body weight.{{cite journal |vauthors=Horváth K, Noker PE, Somfai-Relle S, Glávits R, Financsek I, Schauss AG |date=October 2002 |title=Toxicity of methylsulfonylmethane in rats |journal=Food and Chemical Toxicology |volume=40 |issue=10 |pages=1459–62 |doi=10.1016/S0278-6915(02)00086-8 |pmid=12387309}} Extensive research in animal models indicates MSM has a very low toxicity when administered both orally and topically.{{cite journal |vauthors=Debbi EM, Agar G, Fichman G, Ziv YB, Kardosh R, Halperin N, Elbaz A, Beer Y, Debi R |date=June 2011 |title=Efficacy of methylsulfonylmethane supplementation on osteoarthritis of the knee: a randomized controlled study |journal=BMC Complementary and Alternative Medicine |volume=11 |pages=50 |doi=10.1186/1472-6882-11-50 |pmc=3141601 |pmid=21708034 |doi-access=free}}{{cite journal |last1=Pagonis |first1=Thomas A |name-list-style=vanc |year=2014 |title=The Effect of Methylsulfonylmethane on Osteoarthritic Large Joints and Mobility |url=http://www.ghrnet.org/index.php/ijo/article/view/745/862 |journal=International Journal of Orthopaedics |volume=1 |issue=1 |pages=19–24 |doi=10.6051/j.issn.2311-5106.2014.01.7 |doi-broken-date=1 November 2024}}{{cite journal |vauthors=Takiyama K, Konishi F, Nakashima Y, Mumamoto C |date=2010 |title=Single and 13-week Repeated Oral Dose Toxicity Study of Methylsulfonylmethane in Mice |journal=Oyo Yakuri Pharmacometrics |volume=79 |pages=23–30}} MSM is considered 'Possibly Safe' at therapeutic doses.{{cite web |last=Bauer |first=Brent A. |name-list-style=vanc |date=6 June 2014 |title=MSM for arthritis pain: Is it safe? |url=http://www.mayoclinic.com/health/msm/AN00560 |access-date=14 July 2015 |work=Expert Answers |publisher=Mayo Clinic}}

Nuclear magnetic resonance (NMR) studies have demonstrated that oral doses of MSM are absorbed into the blood and cross the blood/brain barrier.{{cite journal |vauthors=Rose SE, Chalk JB, Galloway GJ, Doddrell DM |date=January 2000 |title=Detection of dimethyl sulfone in the human brain by in vivo proton magnetic resonance spectroscopy |journal=Magnetic Resonance Imaging |volume=18 |issue=1 |pages=95–8 |doi=10.1016/S0730-725X(99)00110-1 |pmid=10642107}}{{cite journal |vauthors=Lin A, Nguy CH, Shic F, Ross BD |date=September 2001 |title=Accumulation of methylsulfonylmethane in the human brain: identification by multinuclear magnetic resonance spectroscopy |journal=Toxicology Letters |volume=123 |issue=2–3 |pages=169–77 |doi=10.1016/S0378-4274(01)00396-4 |pmid=11641045}} An NMR study has also found detectable levels of MSM normally present in the blood and cerebrospinal fluid, suggesting that it derives from dietary sources, intestinal bacterial metabolism, and the body's endogenous methanethiol metabolism.{{cite journal |vauthors=Engelke UF, Tangerman A, Willemsen MA, Moskau D, Loss S, Mudd SH, Wevers RA |date=August 2005 |title=Dimethyl sulfone in human cerebrospinal fluid and blood plasma confirmed by one-dimensional (1)H and two-dimensional (1)H-(13)C NMR |journal=NMR in Biomedicine |volume=18 |issue=5 |pages=331–6 |doi=10.1002/nbm.966 |pmid=15996001 |s2cid=34324509}}

The mechanism of action underlying MSM's medical claims is not clear. Some promoters suggest that most people do not consume enough sulfur. There is no Dietary Reference Intake (DRI) or Daily Value established for sulfur, but it is present in significant amounts in foods such as cruciferous vegetables, garlic, onions, asafoetida, legumes, nuts, seeds, plant milk, animal milk and eggs (both whites and yolks).{{cite web | first = Kerry L. | last = Lang | name-list-style = vanc | url = http://www.quackwatch.org/01QuackeryRelatedTopics/DSH/msm.html |title=Methylsulfonylmethane (MSM) |work=Quackwatch |date=17 June 2001 |access-date=2011-03-12}} The claims for the need for sulfur supplementation originate with Robert Herschler, a biochemist who filed a patent for using MSM as a dietary supplement in 1982.{{cite patent |country= US |number= 4514421 |status= granted |title= Dietary and pharmaceutical uses of methylsulfonylmethane and compositions comprising it |pubdate= |gdate= 30 April 1985 |fdate= |pridate= |inventor= Herschler RJ |assign1=}}

Moreover, in cases involving topical therapeutics, the role of MSM as an active agent, per se, versus its having a role in promoting skin permeation (in manner, akin to its solvent relative DMSO) must be characterized/controlled.{{cite journal |last1=Shanmugam |first1=Srinivasan |last2=Baskaran |first2=Rengarajan |last3=Nagayya-Sriraman |first3=Santhoshkumar |last4=Yong |first4=Chul-Soon |last5=Choi |first5=Han-Gon |last6=Woo |first6=Jong-Soo |last7=Yoo |first7=Bong-Kyu | name-list-style = vanc |title=The Effect of Methylsulfonylmethane on Hair Growth Promotion of Magnesium Ascorbyl Phosphate for the Treatment of Alopecia |journal= Biomolecules and Therapeutics|date=31 July 2009 |volume=17 |issue=3 |pages=241–248 |doi=10.4062/biomolther.2009.17.3.241|doi-access=free}}

The biochemical effects of supplemental methylsulfonylmethane are poorly understood. Some researchers have suggested that MSM has anti-inflammatory effects.

The spectrum of biological effects of dimethyl sulfoxide (DMSO) and MSM differ, but those of DMSO may be mediated, at least in part, by MSM.{{cite journal | vauthors = Kocsis JJ, Harkaway S, Snyder R | title = Biological effects of the metabolites of dimethyl sulfoxide | journal = Annals of the New York Academy of Sciences | volume = 243 | issue = 1 | pages = 104–9 | date = January 1975 | pmid = 1055534 | doi = 10.1111/j.1749-6632.1975.tb25349.x | bibcode = 1975NYASA.243..104K | s2cid = 45625081}}

The first scientific investigation of MSM for skin health was published in 2015. The RCT used a 3g per day dose and included only 20 women. Results showed significant improvements in the number and severity of facial wrinkles, firmness, tone and texture.{{Cite journal |last1=Anthonavage |first1=Michael |last2=Benjamin |first2=Rod |last3=Withee |first3=Eric |date=2015 |title=Effects of oral supplementation with methylsulfonylmethane on skin health and wrinkle reduction |url=https://www.naturalmedicinejournal.com/journal/2015-11/effects-oral-supplementation-methylsulfonylmethane-skin-health-and-wrinkle-reduction |journal=Natural Medicine Journal |volume=7 |issue=11 |pages=1–21}} Another study evaluated doses of 1g and 3g and showed improvements in wrinkles, firmness, and hydration at both dose levels in 20 persons.{{Cite journal |last1=Muizzuddin |first1=Neelam |last2=Benjamin |first2=Rodney |date=2020-02-21 |title=Beauty from within: Oral administration of a sulfur-containing supplement methylsulfonylmethane improves signs of skin ageing |journal=International Journal for Vitamin and Nutrition Research |language=en |volume=92 |issue=3–4 |pages=182–191 |doi=10.1024/0300-9831/a000643 |issn=0300-9831 |pmid=32083522 |s2cid=211232166 |doi-access=free}} The same author published a study on MSM for hair and nails from the same clinical trial. The results showed improvements in hair shine, volume, and appearance, and nail shine and appearance.{{Cite journal |last1=Muizzuddin |first1=Neelam |last2=Benjamin |first2=Rodney |date=2019 |title=Beneficial Effects of a Sulfur-Containing Supplement on Hair and Nail Condition |url=https://www.naturalmedicinejournal.com/journal/2019-11/beneficial-effects-sulfur-containing-supplement-hair-and-nail-condition |journal=Natural Medicine Journal |volume=11 |issue=11 |pages=1–8}} An Italian study evaluated the effects of a nutraceutical composed of MSM, hyaluronic acid, and L-carnosine. The results from RCT showed broad improvements in facial skin hydration and elasticity, as well as decreased sebaceous secretions.{{Cite journal |last1=Guaitolini |first1=Ennio |last2=Cavezzi |first2=Attilio |last3=Cocchi |first3=Stefania |last4=Colucci |first4=Roberto |last5=Urso |first5=Simone Ugo |last6=Quinzi |first6=Valentina |date=2019 |title=Randomized, Placebo-controlled Study of a Nutraceutical Based on Hyaluronic Acid, L-carnosine, and Methylsulfonylmethane in Facial Skin Aesthetics and Well-being |journal=The Journal of Clinical and Aesthetic Dermatology |volume=12 |issue=4 |pages=40–45 |issn=1941-2789 |pmc=6508480 |pmid=31119010}}

In one small human trial, MSM has been shown to protect muscles from damage by reducing the amount of oxidative stress damage incurred through exercise.{{cite journal |vauthors=Barmaki S, Bohlooli S, Khoshkhahesh F, Nakhostin-Roohi B |date=April 2012 |title=Effect of methylsulfonylmethane supplementation on exercise - Induced muscle damage and total antioxidant capacity |url=http://www.minervamedica.it/index2.t?show=R40Y2012N02A0170 |journal=The Journal of Sports Medicine and Physical Fitness |volume=52 |issue=2 |pages=170–4 |pmid=22525653}}{{cite journal |vauthors=Nakhostin-Roohi B, Barmaki S, Khoshkhahesh F, Bohlooli S |date=October 2011 |title=Effect of chronic supplementation with methylsulfonylmethane on oxidative stress following acute exercise in untrained healthy men |url=http://eprints.arums.ac.ir/2588/1/chronic.pdf |journal=The Journal of Pharmacy and Pharmacology |volume=63 |issue=10 |pages=1290–4 |doi=10.1111/j.2042-7158.2011.01314.x |pmid=21899544 |s2cid=25474694}} In a second small trial the total antioxidant capacity was significantly increased after taking MSM.{{cite journal |vauthors=Nakhostin-Roohi B, Niknam Z, Vaezi N, Mohammadi S, Bohlooli S |year=2013 |title=Effect of single dose administration of methylsulfonylmethane on oxidative stress following acute exhaustive exercise |journal=Iranian Journal of Pharmaceutical Research |volume=12 |issue=4 |pages=845–53 |pmc=3920715 |pmid=24523764}} Studies in animals indicate a hepatoprotective effect of MSM against several toxins including acetaminophen, paraquat, and carbon tetrachloride.{{cite journal |vauthors=Bohlooli S, Mohammadi S, Amirshahrokhi K, Mirzanejad-Asl H, Yosefi M, Mohammadi-Nei A, Chinifroush MM |date=August 2013 |title=Effect of Methylsulfonylmethane Pretreatment on Aceta-minophen Induced Hepatotoxicity in Rats |journal=Iranian Journal of Basic Medical Sciences |volume=16 |issue=8 |pages=896–900 |pmc=3786100 |pmid=24106592}}{{cite journal |vauthors=Amirshahrokhi K, Bohlooli S |date=October 2013 |title=Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice |journal=Inflammation |volume=36 |issue=5 |pages=1111–21 |doi=10.1007/s10753-013-9645-8 |pmid=23595869 |s2cid=2209805}}{{cite journal |vauthors=Kamel R, El Morsy EM |date=September 2013 |title=Hepatoprotective effect of methylsulfonylmethane against carbon tetrachloride-induced acute liver injury in rats |journal=Archives of Pharmacal Research |volume=36 |issue=9 |pages=1140–8 |doi=10.1007/s12272-013-0110-x |pmid=23591777 |s2cid=27990171}}{{cite journal |last1=Disilvestro |first1=Robert A |last2=Disilvestro |first2=David J |last3=Disilvestro |first3=Daniel J |name-list-style=vanc |date=2008 |title=Methylsulfonylmethane (MSM) Intake in Mice Produces Elevated Liver Glutathione and Partially Protects Against Carbon Tetrachloride-Induced Liver Injury |journal=FASEB J. |volume=22 |issue=1 |pages=445–8 |doi=10.1096/fasebj.22.1_supplement.445.8 |s2cid=84049802 |doi-access=free}} Animal models of experimental colitis and pulmonary hypertension indicate a protective effect as well.{{cite journal |vauthors=Amirshahrokhi K, Bohlooli S, Chinifroush MM |date=June 2011 |title=The effect of methylsulfonylmethane on the experimental colitis in the rat |journal=Toxicology and Applied Pharmacology |volume=253 |issue=3 |pages=197–202 |bibcode=2011ToxAP.253..197A |doi=10.1016/j.taap.2011.03.017 |pmid=21463646}}{{cite journal |vauthors=Mohammadi S, Najafi M, Hamzeiy H, Maleki-Dizaji N, Pezeshkian M, Sadeghi-Bazargani H, Darabi M, Mostafalou S, Bohlooli S, Garjani A |year=2012 |title=Protective effects of methylsulfonylmethane on hemodynamics and oxidative stress in monocrotaline-induced pulmonary hypertensive rats |journal=Advances in Pharmacological Sciences |volume=2012 |pages=1–6 |doi=10.1155/2012/507278 |pmc=3478703 |pmid=23118745 |doi-access=free}}

Two studies have evaluated the effects of MSM on allergic rhinitis. A 2004 multi-centered, open-label clinical trial found that MSM reduced both upper and lower respiratory symptoms associated with seasonal allergic rhinitis (SAR), and increased energy levels. It found no significant changes in IgE levels, although the duration of the study was not likely long enough to see changes.{{Cite journal |last1=Barrager |first1=Eleanor |last2=Veltmann |first2=Joseph R. |last3=Schauss |first3=Alexander G. |last4=Schiller |first4=Rebecca N. |date=2002 |title=A Multicentered, Open-Label Trial on the Safety and Efficacy of Methylsulfonylmethane in the Treatment of Seasonal Allergic Rhinitis |journal=The Journal of Alternative and Complementary Medicine |language=en |volume=8 |issue=2 |pages=167–173 |doi=10.1089/107555302317371451 |issn=1075-5535 |pmid=12006124}} An RCT evaluated three doses of MSM and found that a 3g daily dose was most effective compared to 1g or 6g per day. Daily use at 3g decreased allergy-associated symptoms, including itchy eyes, itchy nose, watery eyes, rhinorrhea, sneezing, and nasal obstruction. The 3g dose also improved peak nasal inspiratory flow (PNIF) indicating improved breathing. The study also evaluated an acute 12g dose and found significant improvements in all symptoms except itching eyes and sneezing, but not for PNIF.{{Cite journal |last1=Hewlings |first1=Susan |last2=Kalman |first2=Douglas S |date=2018-11-29 |title=Evaluating the Impacts of Methylsulfonylmethane on Allergic Rhinitis After a Standard Allergen Challenge: Randomized Double-Blind Exploratory Study |journal=JMIR Research Protocols |language=en |volume=7 |issue=11 |pages=e11139 |doi=10.2196/11139 |issn=1929-0748 |pmc=6293242 |pmid=30497995 |doi-access=free}}

MSM has been shown to improve immune function markers. RCT found that in blood samples taken after bouts of exhaustive exercise, there was a reduced response to an infectious stimulus in the placebo group, but the MSM group maintained a robust response, indicating that MSM protected against stress-induced immunosuppression. The authors postulate that MSM’s anti-inflammatory properties reduce the overstimulation of inflammatory cells during exercise, thus conserving their ability to respond to infections threats.{{Cite journal |last1=van der Merwe |first1=Mariè |last2=Bloomer |first2=Richard J. |date=2016 |title=The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise |journal=Journal of Sports Medicine |language=en |volume=2016 |pages=7498359 |doi=10.1155/2016/7498359 |issn=2356-7651 |pmc=5097813 |pmid=27844051 |doi-access=free}} This is supported by in vitro research showing MSM inhibits over-activation of white blood cells and has an anti-apoptotic effect.{{Cite journal |last1=Kim |first1=Yoon Hee |last2=Kim |first2=Dae Hwan |last3=Lim |first3=Hwan |last4=Baek |first4=Doo-Yeon |last5=Shin |first5=Hyun-Kyung |last6=Kim |first6=Jin-Kyung |date=2009 |title=The anti-inflammatory effects of methylsulfonylmethane on lipopolysaccharide-induced inflammatory responses in murine macrophages |journal=Biological & Pharmaceutical Bulletin |volume=32 |issue=4 |pages=651–656 |doi=10.1248/bpb.32.651 |issn=0918-6158 |pmid=19336900 |doi-access=free}}{{Cite journal |last1=Karabay |first1=Arzu Z. |last2=Aktan |first2=Fugen |last3=Sunguroğlu |first3=Asuman |last4=Buyukbingol |first4=Zeliha |date=2014 |title=Methylsulfonylmethane modulates apoptosis of LPS/IFN-γ-activated RAW 264.7 macrophage-like cells by targeting p53, Bax, Bcl-2, cytochrome c and PARP proteins |journal=Immunopharmacology and Immunotoxicology |language=en |volume=36 |issue=6 |pages=379–389 |doi=10.3109/08923973.2014.956752 |issn=0892-3973 |pmid=25211405 |s2cid=29105910}}

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Category:Dietary supplements

Category:Experimental medical treatments

Category:Solvents

Category:Sulfones

Category:Food additives

Category:Methyl compounds